My overall objective is to contribute to the understanding of how gene expression is normally controlled and why expression of specific genes is deranged in different human genetic diseases. The specific studies proposed should furnish information on the extent to which extrapolation from the globin gene system can be made to other eukaryotic gene systems such as the growth hormone system. To do this, using recombinant DNA techniques (restricting mapping, cloning, and nucleotide sequencing) I will study the 1) linkage 2) chromosomal locations, 3) number of loci, 4) allelic forms, and the 5) relationship between DNA modification (methylation) and gene expression of the human growth hormone (hGH) and chorionic somatomammotropin (hCS) genes. These results will provide insight into how basic genes structure and expression normally correspond in analogous eukaryotic systems. The molecular defects previously characterized in globin genes will provide a foundation for examining the hGH and hCS genes in analogous disorders of gene expression. In addition, I will continue to analyze defects of globin genes and improve methods for prenatal detection of severe disorders of globin gene expression (sickle cell anemia and the beta-thalassemias).